Necroptosis protects against exacerbation of acute pancreatitis

• Material Type: 博士論文
• Title: Necroptosis protects against exacerbation of acute pancreatitis
• Author/Editor: Boonchan, Michittra; Arimochi, Hideki; Otsuka, Kunihiro; Kobayashi, Tomoko; Uehara, Hisanori; Jaroonwitchawan, Thiranut; Sasaki, Yuki; Tsukumo, Shin-ichi; Yasutomo, Koji
• Author Heading: Boonchan, Michittra; Arimochi, Hideki; Otsuka, Kunihiro; Kobayashi, Tomoko; Uehara, Hisanori; Jaroonwitchawan, Thiranut; Sasaki, Yuki; Tsukumo, Shin-ichi; Yasutomo, Koji
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2021-06-10
• Publication Date (W3CDTF): 2021-06-10
• Alternative Title: ネクロプトーシスは急性膵炎の悪化を防ぐ; Necroptosis and acute pancreatitis
• Periodical title: Cell Death & Disease
• No. or year of volume/issue: 12
• Volume: 12
• Pages: 601-
• ISSN (Periodical Title): ISSN : 2041-4889
• Degree grantor/type: 徳島大学
• Date Granted: 2021-09-09
• Dissertation Number: 甲第3539号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: ネクロプトーシス; 急性膵炎; MLKL; RIPK3; 遺伝子欠損マウス
• Target Audience: 一般
• Note (General): The sensing of various extrinsic stimuli triggers the receptor-interacting protein kinase-3 (RIPK3)-mediated signaling pathway, which leads to mixed-lineage kinase-like (MLKL) phosphorylation followed by necroptosis. Although necroptosis is a form of cell death and is involved in inflammatory conditions, the roles of necroptosis in acute pancreatitis (AP) remain unclear. In the current study, we administered caerulein to Ripk3- or Mlkl-deficient mice (Ripk3-/- or Mlkl-/- mice, respectively) and assessed the roles of necroptosis in AP. We found that Ripk3-/- mice had significantly more severe pancreatic edema and inflammation associated with macrophage and neutrophil infiltration than control mice. Consistently, Mlkl-/- mice were more susceptible to caerulein-induced AP, which occurred in a time- and dose-dependent manner, than control mice. Mlkl-/- mice exhibit weight loss, edematous pancreatitis, necrotizing pancreatitis, and acinar cell dedifferentiation in response to tissue damage. Genetic deletion of Mlkl resulted in downregulation of the antiapoptotic genes Bclxl and Cflar in association with increases in the numbers of apoptotic cells, as detected by TUNEL assay. These findings suggest that RIPK3 and MLKL-mediated necroptosis exerts protective effects in AP and caution against the use of necroptosis inhibitors for AP treatment.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Related Material (DOI): 10.1038/s41419-021-03847-w
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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http://repo.lib.tokushima-u.ac.jp/files/public/11/116381/20211005131836752664/k3539_abstract_review.pdf fulltext

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